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Translational Research: the Journal of Laboratory and Clinical Medicine

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https://www.readbyqxmd.com/read/29040818/metformin-attenuates-er-stress-induced-mitochondrial-dysfunction
#1
Qun Chen, Jeremy Thompson, Ying Hu, Anindita Das, Edward J Lesnefsky
Endoplasmic reticulum (ER) stress, a disturbance of the ER function, contributes to cardiac injury. ER and mitochondria are closely connected organelles within cells. ER stress contributes to mitochondrial dysfunction, which is a key factor to increase cardiac injury. Metformin, a traditional anti-diabetic drug, decreases cardiac injury during ischemia-reperfusion. Metformin also inhibits ER stress in cultured cells. We hypothesized that metformin can attenuate the ER stress-induced mitochondrial dysfunction and subsequent cardiac injury...
September 28, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28993096/altered-expression-of-malat1-lncrna-in-nonalcoholic-steatohepatitis-fibrosis-regulates-cxcl5-in-hepatic-stellate-cells
#2
Fatjon Leti, Christophe Legendre, Christopher D Still, Xin Chu, Anthony Petrick, Glenn S Gerhard, Johanna K DiStefano
In the present study, we sought to identify long noncoding RNA (lncRNA) expression profiles in nonalcoholic steatohepatitis (NASH) patients with histologic evidence of lobular inflammation and advanced fibrosis. We profiled lncRNA expression using RNA-sequencing of wedge liver biopsies from 24 nonalcoholic fatty liver disease (NAFLD) patients with normal liver histology, 53 NAFLD patients with lobular inflammation, and 65 NAFLD patients with advanced fibrosis. Transcript profiling identified 4432 and 4057 differentially expressed lncRNAs in comparisons of normal tissue with lobular inflammation and fibrosis samples, respectively...
September 19, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28919341/metabolic-programming-of-the-epigenome-host-and-gut-microbial-metabolite-interactions-with-host-chromatin
#3
REVIEW
Kimberly A Krautkramer, Rashpal S Dhillon, John M Denu, Hannah V Carey
The mammalian gut microbiota has been linked to host developmental, immunologic, and metabolic outcomes. This collection of trillions of microbes inhabits the gut and produces a myriad of metabolites, which are measurable in host circulation and contribute to the pathogenesis of human diseases. The link between endogenous metabolite availability and chromatin regulation is a well-established and active area of investigation; however, whether microbial metabolites can elicit similar effects is less understood...
September 1, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28873345/neutrophil-chemotaxis-and-transcriptomics-in-term-and-preterm-neonates
#4
Steven L Raymond, Brittany J Mathias, Tyler J Murphy, Jaimar C Rincon, María Cecilia López, Ricardo Ungaro, Felix Ellett, Julianne Jorgensen, James L Wynn, Henry V Baker, Lyle L Moldawer, Daniel Irimia, Shawn D Larson
Neutrophils play a crucial role in combating life-threatening bacterial infections in neonates. Previous studies investigating neonatal cell function have been limited because of restricted volume sampling. Here, using novel microfluidic approaches, we provide the first description of neutrophil chemotaxis and transcriptomics from whole blood of human term and preterm neonates, as well as young adults. Ex vivo percent cell migration, neutrophil velocity, and directionality to N-formylmethionyl-leucyl-phenylalanine were measured from whole blood using time-lapse imaging of microfluidic chemotaxis...
September 1, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28917654/the-anticancer-functions-of-rig-i-like-receptors-rig-i-and-mda5-and-their-applications-in-cancer-therapy
#5
REVIEW
Yuanbing Wu, Xinqiang Wu, Longhuo Wu, Xiangcai Wang, Zhiping Liu
Cancer is a major cause of death worldwide, and its incidence and mortality continuously increase in China. Nowadays, cancer heavily influences our health and constitutes enormous burden on society and families. Although there are many tools for cancer treatment, but the overall therapeutic effect is poor. In addition, cancer cells often develop resistance to therapy due to defective cell death or immune escape mechanisms. Therefore, it is a promising way for cancer treatment to effectively activate apoptosis and conquer immunosuppression...
August 31, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28802867/novel-single-cell-technologies-in-acute-myeloid-leukemia-research
#6
REVIEW
Soumyasri Das Gupta, Zohar Sachs
Acute myeloid leukemia (AML) is a lethal malignancy because patients who initially respond to chemotherapy eventually relapse with treatment refractory disease. Relapse is caused by leukemia stem cells (LSCs) that reestablish the disease through self-renewal. Self-renewal is the ability of a stem cell to produce copies of itself and give rise to progeny cells. Therefore, therapeutic strategies eradicating LSCs are essential to prevent relapse and achieve long-term remission in AML. AML is a heterogeneous disease both at phenotypic and genotypic levels, and this heterogeneity extends to LSCs...
July 25, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28784428/large-scale-3-dimensional-quantitative-imaging-of-tissues-state-of-the-art-and-translational-implications
#7
REVIEW
Seth Winfree, Michael J Ferkowicz, Pierre C Dagher, Katherine J Kelly, Michael T Eadon, Timothy A Sutton, Troy A Markel, Mervin C Yoder, Kenneth W Dunn, Tarek M El-Achkar
Recent developments in automated optical sectioning microscope systems have enabled researchers to conduct high resolution, three-dimensional (3D) microscopy at the scale of millimeters in various types of tissues. This powerful technology allows the exploration of tissues at an unprecedented level of detail, while preserving the spatial context. By doing so, such technology will also enable researchers to explore cellular and molecular signatures within tissue and correlate with disease course. This will allow an improved understanding of pathophysiology and facilitate a precision medicine approach to assess the response to treatment...
July 22, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28867395/nanoformulated-copper-zinc-superoxide-dismutase-exerts-differential-effects-on-glucose-vs-lipid-homeostasis-depending-on-the-diet-composition-possibly-via-altered-ampk-signaling
#8
Gopalakrishnan Natarajan, Curtis Perriotte-Olson, Fatema Bhinderwala, Robert Powers, Cyrus V Desouza, Geoffrey A Talmon, Jiang Yuhang, Matthew C Zimmerman, Alexander V Kabanov, Viswanathan Saraswathi
Evidence suggests that superoxide dismutase 1 (SOD1) promotes glucose vs lipid metabolism depending on the diet type. We recently reported that nanoformulated SOD1 (Nano) improved lipid metabolism without altering glucose homeostasis in high-fat (HF) diet-fed mice. Here, we sought to determine the effects and potential mechanisms of Nano in modulating glucose and lipid homeostasis in mice fed a normal chow diet (CD) vs HF diet. Mice were fed a CD or a HF diet (45%) for 10 wk and injected with Nano once every 2 days for 15 days...
October 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28860053/blood-brain-barrier-adapted-precision-medicine-therapy-for-pediatric-brain-tumors
#9
Bernard L Marini, Lydia L Benitez, Andrew H Zureick, Ralph Salloum, Angela C Gauthier, Julia Brown, Yi-Mi Wu, Dan R Robinson, Chandan Kumar, Robert Lonigro, Pankaj Vats, Xuhong Cao, Katayoon Kasaian, Bailey Anderson, Brendan Mullan, Benjamin Chandler, Joseph R Linzey, Sandra I Camelo-Piragua, Sriram Venneti, Paul E McKeever, Kathryn A McFadden, Andrew P Lieberman, Noah Brown, Lina Shao, Marcia A S Leonard, Larry Junck, Erin McKean, Cormac O Maher, Hugh J L Garton, Karin M Muraszko, Shawn Hervey-Jumper, Jean M Mulcahy-Levy, Adam Green, Lindsey M Hoffman, Katie Dorris, Nicholas A Vitanza, Joanne Wang, Jonathan Schwartz, Rishi Lulla, Natasha Pillay Smiley, Miriam Bornhorst, Daphne A Haas-Kogan, Patricia L Robertson, Arul M Chinnaiyan, Rajen Mody, Carl Koschmann
Targeted chemotherapeutics provide a promising new treatment option in neuro-oncology. The ability of these compounds to penetrate the blood-brain barrier is crucial for their successful incorporation into patient care. "CNS Targeted Agent Prediction" (CNS-TAP) is a multi-institutional and multidisciplinary translational program established at the University of Michigan for evaluating the central nervous system (CNS) activity of targeted therapies in neuro-oncology. In this report, we present the methodology of CNS-TAP in a series of pediatric and adolescent patients with high-risk brain tumors, for which molecular profiling (academic and commercial) was sought and targeted agents were incorporated...
October 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28797549/predicting-thyroid-nodule-malignancy-at-several-prevalence-values-with-a-combined-bethesda-molecular-test
#10
Hélène Lasolle, Benjamin Riche, Myriam Decaussin-Petrucci, Emmanuelle Dantony, Véronique Lapras, Catherine Cornu, Joël Lachuer, Jean-Louis Peix, Jean-Christophe Lifante, Oana-Maria Capraru, Samia Selmi-Ruby, Bernard Rousset, Françoise Borson-Chazot, Pascal Roy
Investigation of thyroid nodules using fine-needle aspiration cytology (FNAC) gives indeterminate results in up to 30% of samples using the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). We present a combined Bethesda-molecular predictor of nodule malignancy to improve the accuracy of the preoperative diagnosis of thyroid nodules. To detect a molecular signature of thyroid nodule malignancy, a molecular test was performed on FNACs from 128 thyroid nodules from prospectively included patients, collected in a tertiary center...
October 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28754419/evaluation-of-tolerance-to-lentiviral-lv-rpe65-gene-therapy-vector-after-subretinal-delivery-in-non-human-primates
#11
Alexandre Matet, Corinne Kostic, Alexis-Pierre Bemelmans, Alexandre Moulin, Serge G Rosolen, Samia Martin, Fulvio Mavilio, Vazrik Amirjanians, Knut Stieger, Birgit Lorenz, Francine Behar-Cohen, Yvan Arsenijevic
Several approaches have been developed for gene therapy in RPE65-related Leber congenital amaurosis. To date, strategies that have reached the clinical stages rely on adeno-associated viral vectors and two of them documented limited long-term effect. We have developed a lentiviral-based strategy of RPE65 gene transfer that efficiently restored protein expression and cone function in RPE65-deficient mice. In this study, we evaluated the ocular and systemic tolerances of this lentiviral-based therapy (LV-RPE65) on healthy nonhuman primates (NHPs), without adjuvant systemic anti-inflammatory prophylaxis...
October 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28719799/mesencephalic-astrocyte-derived-neurotrophic-factor-manf-a-new-player-in-endoplasmic-reticulum-diseases-structure-biology-and-therapeutic-roles
#12
REVIEW
Yeawon Kim, Sun-Ji Park, Ying Maggie Chen
Mesencephalic astrocyte-derived neurotrophic factor (MANF), a newly identified 18-kDa soluble protein, localizes to the luminal endoplasmic reticulum (ER), whose stress can stimulate MANF expression and secretion. In Drosophila and zebrafish, MANF regulates dopaminergic neuron development. In contrast, in mice, MANF deficiency leads to diabetes and activation of the unfolded protein response. Recent studies in rodent models have demonstrated that MANF mitigates diabetes, exerts neurotrophic function in neurodegenerative disease, protects cardiomyocytes and neurons in myocardial infarction and cerebral ischemia, respectively, and promotes immune cell phenotype switch from proinflammatory macrophages to prorepair anti-inflammatory macrophages...
October 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27931982/jak-inhibitor-tofacitinib-suppresses-interferon-alfa-production-by-plasmacytoid-dendritic-cells-and-inhibits-arthrogenic-and-antiviral-effects-of-interferon-alfa
#13
Patrick P C Boor, Petra E de Ruiter, Patrick S Asmawidjaja, Erik Lubberts, Luc J W van der Laan, Jaap Kwekkeboom
Tofacitinib is an oral Janus kinase inhibitor that is effective for the treatment of rheumatoid arthritis and shows encouraging therapeutic effects in several other autoimmune diseases. A prominent adverse effect of tofacitinib therapy is the increased risk of viral infections. Despite its advanced stage of clinical development, the modes of action that mediate the beneficial and adverse effects of tofacitinib in autoimmune diseases remain unclear. Interferon alfa (IFNα) produced by plasmacytoid dendritic cells (PDCs) is critically involved in the pathogenesis of many systemic autoimmune diseases and in immunity to viral infections...
October 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/26972567/phase-1-2-pilot-clinical-trial-in-patients-with-decompensated-liver-cirrhosis-treated-with-bone-marrow-derived-endothelial-progenitor-cells
#14
Delia D'Avola, Verónica Fernández-Ruiz, Francisco Carmona-Torre, Miriam Méndez, Javier Pérez-Calvo, Felipe Prósper, Enrique Andreu, José Ignacio Herrero, Mercedes Iñarrairaegui, Carmen Fuertes, José Ignacio Bilbao, Bruno Sangro, Jesús Prieto, Jorge Quiroga
The aim of this nonrandomized, open label, phase 1 clinical trial was to evaluate the safety and the feasibility of the treatment with autologous bone marrow-derived endothelial progenitor cells (EPC) in decompensated liver cirrhosis. In addition, the changes in liver function and hepatic venous pressure gradient (HVPG) and their relation with the characteristics of the cellular product were analyzed. Twelve patients with Child-Pugh ≥8 liver cirrhosis underwent bone marrow harvest for ex vivo differentiation of EPC...
October 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/26845626/contribution-of-glutaredoxin-1-to-s-glutathionylation-of-endothelial-nitric-oxide-synthase-for-mesenteric-nitric-oxide-generation-in-experimental-necrotizing-enterocolitis
#15
Qingjuan Shang, Lei Bao, Hongjie Guo, Fabao Hao, Qianfu Luo, Jiaping Chen, Chunbao Guo
Endothelial nitric oxide synthase (eNOS) is critical for intestinal microcirculatory perfusion and therefore plays a key role in the development of necrotizing enterocolitis (NEC). eNOS-derived nitric oxide (NO) is inhibited by S-glutathionylation of eNOS (eNOS-SSG), which can be reversed by glutaredoxin-1 (Grx1). Therefore, the objective of this study was to investigate the interplay between Grx1 and eNOS in regulating the following inflammation signal during the development of NEC. Primary mouse intestinal microvascular endothelial cells (MIMECs) and peritoneal macrophages were subjected to lipopolysaccharide treatment, and Grx1-/- mice were subjected to an NEC-inducing regimen of formula feeding in combination with hypoxia and hypothermia...
October 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28755873/chimeric-antigen-receptor-t-cell-therapy-for-glioblastoma
#16
REVIEW
Analiz Rodriguez, Christine Brown, Behnam Badie
Chimeric antigen receptor (CAR) T-cell therapy has shown great promise in the treatment of hematological disease, and its utility for treatment of solid tumors is beginning to unfold. Glioblastoma continues to portend a grim prognosis and immunotherapeutic approaches are being explored as a potential treatment strategy. Identification of appropriate glioma-associated antigens, barriers to cell delivery, and presence of an immunosuppressive microenvironment are factors that make CAR T-cell therapy for glioblastoma particularly challenging...
September 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28755872/new-approaches-for-the-enhancement-of-chimeric-antigen-receptors-for-the-treatment-of-hiv
#17
REVIEW
Mayra A Carrillo, Anjie Zhen, Jerome A Zack, Scott G Kitchen
HIV infection continues to be a life-long chronic disease in spite of the success of antiretroviral therapy (ART) in controlling viral replication and preventing disease progression. However, because of the high cost of treatment, severe side effects, and inefficiency in curing the disease with ART, there is a call for alternative therapies that will provide a functional cure for HIV. Cytotoxic T lymphocytes (CTLs) are vital in the control and clearance of viral infections and therefore immune-based therapies have attempted to engineer HIV-specific CTLs that would be able to clear the infection from the body...
September 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28719798/chimeric-antigen-receptor-t-cells-for-b-cell-malignancies
#18
REVIEW
Eben I Lichtman, Gianpietro Dotti
The adoptive transfer of T-lymphocytes modified to express chimeric antigen receptors (CAR-Ts) has produced impressive clinical responses among patients with B-cell malignancies. This has led to a rapid expansion in the number of clinical trials over the past several years. Although CD19-specific CAR-Ts are the most extensively evaluated, CAR-Ts specific for other B-cell-associated targets have also shown promise. However, despite this success, toxicities associated with CAR-T administration remain a significant concern...
September 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28688236/antigen-specific-regulatory-t-cells-are-police-cars-the-answer
#19
REVIEW
Nicholas A J Dawson, Megan K Levings
Cellular therapy with T-regulatory cells (Tregs) is a promising strategy to control immune responses and restore immune tolerance in a variety of immune-mediated diseases, such as transplant rejection and autoimmunity. Multiple clinical trials are currently testing this approach, typically by infusing a single dose of polyclonal Tregs that have been expanded in vitro. However, evidence from animal models of Treg therapy has clearly shown that antigen-specific Tregs are vastly superior to polyclonal cells, meaning that fewer cells are needed for the desired therapeutic effect...
September 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28651074/chimeric-antigen-receptor-engineered-natural-killer-and-natural-killer-t-cells-for-cancer-immunotherapy
#20
REVIEW
Dominique Bollino, Tonya J Webb
Natural killer (NK) cells of the innate immune system and natural killer T (NKT) cells, which have roles in both the innate and adaptive responses, are unique lymphocyte subsets that have similarities in their functions and phenotypes. Both cell types can rapidly respond to the presence of tumor cells and participate in immune surveillance and antitumor immune responses. This has incited interest in the development of novel cancer therapeutics based on NK and NKT cell manipulation. Chimeric antigen receptors (CARs), generated through the fusion of an antigen-binding region of a monoclonal antibody or other ligand to intracellular signaling domains, can enhance lymphocyte targeting and activation toward diverse malignancies...
September 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
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